From Terbutaline to Vagus Nerve S5mula5on – Treat Wheezing like a Pro! David Robinson, MD Joanne L. Oakes, MD Objec5ves: All That Wheezes •  Discuss best evidence ED treatment op5ons for acute COPD vs. asthma exacerba5ons •  Compare the u5lity of non-‐invasive ven5la5on for acute COPD vs. asthma exacerba5ons •  Compare and contrast new vs. standard treatment op5ons for acute exacerba5ons presen5ng to the ED I have no ﬁnancial or other rela5onship disclosures to report. Pa5ent Number One… •  Cri5cal care room 1 •  6 year old boy •  BMI 35, H/O severe uncontrolled asthma •  Anxious, speaks in phrases •  RR 40, poor air movement, SpO2 88% •  Inspiratory and expiratory wheezes, subcostal and intercostal retrac5ons Pa5ent Number Two… Cri5cal care room 2 65 year old man Long term smoker “Can’t breathe”, new purulent sputum x 3 days, out of home O2 •  Afebrile •  RR 40, poor air movement, SpO2 88% • 
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There is one ICU bed •  Who is sicker? •  Intuba5on vs. Non-‐invasive ven5la5on? •  Throw everything in “the kitchen sink” at both? What’s not new… • 
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β2-‐agonists Oral vs. IV steroids for acute exacerba5ons Racial, urban*, and rural healthcare dispari5es Wide prac5ce varia5on and guideline adherence Asthma •  Only 2 completely new classes of drugs approved since the 1960s •  Leukotriene receptor antagonists (LTRAs) 1997: Montelukast (Singulair)*, Zaﬁrlukast (Accolate) •  Recombinant humanized monoclonal an5body against IgE: Omalizumab (Xolair) •  Neither of these classes are indicated for acute exacerba5ons •  Inhaled cor5costeroids (ICS) and B-‐agonists remain the cornerstones of therapy with other medica5ons added on in “steps” Outpa5ent Asthma Management hnp://www.sciencedirect.com/science/ar5cle/pii/S0165614710000787 Some (Data-‐Driven) Thoughts to Consider: •  Guideline use is proven to improve outcomes •  Poor outpa5ent compliance cited in mul5ple studies •  Outpa5ent noncompliance drives ED visits and hospitaliza5ons •  Early administra5on of steroids (<60 minutes) reduces hospital admission rates for children with moderate and severe exacerba5on Bhogal, et al; Shan, et al; Papierniak et al; Edwards, et al Some (Data-‐Driven) Thoughts to Consider: •  An5bio5cs: Not helpful unless acute infec5on •  Ongoing studies regarding long term an5-‐inﬂammatory beneﬁts for certain pa5ent subsets •  Magnesium sulfate in asthma: •  Children: IV improves pulmonary func5on and reduces number of hospital admissions •  Adults: IV improves pulmonary func5on only •  Nebulized appears to produce beneﬁts for adults only Bhogal, et al; Shan, et al; Papierniak et al; Edwards, et al Why Use Guidelines at all? Which one? Gorelick MH, Stevens MW, Schultz TR, et al. Performance of a Novel Clinical Score, The Pediatric Asthma Severity Score (PASS), in the Evalua5on of Acute Asthma. Acad Emerg Med 2004 11(1): 10-‐18. , hnp://www.childrenscolorado.org/pdf/2009-‐2010-‐Asthma-‐CCG.pdf Dexheimer JW, Abramo TJ, Arnold DH, et al. An asthma management system in a pediatric emergency department. Interna5onal Journal of Medical Informa5cs 2012, hnp://dx.doi.org/10.1016/j.ijmedinf.2012 Dexheimer JW, Abramo TJ, Arnold DH, et al. An asthma management system in a pediatric emergency department. Interna5onal Journal of Medical Informa5cs 2012, hnp://dx.doi.org/10.1016/j.ijmedinf.2012 Adjunct Therapies for Asthma: What’s the Newest (or any old) Evidence? • 
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Subcutaneous or IV Short ac5ng β2-‐agonists Ketamine Heliox Nebulized steroids Theophylline Non-‐invasive ven5la5on… Sellers, WFS. Inhaled and intravenous treatment in acute severe and life-‐threatening asthma. Bri5sh Journal of Anaesthesia 2013 (110) 2: 183-‐90 Asthma: IV Treatment Op5ons Sellers, WFS. Inhaled and intravenous treatment in acute severe and life-‐threatening asthma. Bri5sh Journal of Anaesthesia 2013 (110) 2: 183-‐90 The Jury is S5ll Out… Alternate Therapies for Asthma •  Non-‐invasive ven5la5on: •  +Beneﬁts: shorter ICU and hospital stays, decreased RR and clinical asthma scores •  Sparse data for asthma, beneﬁcial in CHF/COPD •  FDA approved: Bronchial thermoplasty Alternate Therapies for Asthma Bronchial Thermoplasty (BT) •  AIR-‐2 Trial (n=297) – Outpa5ent procedure (x3) – 79% of trial showed QOL beneﬁts with BT (vs 66%) – 32% reduc5on in severe RAD – 84% reduced EM Visits, reduced lost work, school – FDA approved Alternate Therapies for Asthma •  Non-‐FDA approved, under inves5ga5on: •  Interleukin targeted therapies: several phase 2 trials •  Immunomodulators (Omalizumab) •  Tiotropium (Spiriva): inhaled long-‐ac5ng an5-‐
cholingeric bronchodilator •  Possible an5-‐inﬂammatory eﬀects: •  Thiazolidinediones, inhaled furosemide, inhaled heparins, colchicine, cyclosporine A, mycophenolate, methotrexate, IVIG, gold, HMG-‐CoA reductase inhibitors Pulsed Electrical Vagal Nerve S5mulator (VNS) –  Low V Electrode placed at Right caro5d sheath –  60 min of VNS (N=25) Outcome: •  Improved FEV(1) by 15.8% -‐ 27.5% by 60 minutes •  Work of breathing improved 53.9-‐81.0% by 60 min Miner. Acad Emer Med 2012;19:421-‐9 How About A Non-‐Invasive Vagal Nerve S5mulator? Outcome: N=4 • 
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Improved FEV(1) by 9% over 90 minutes VAS score for eﬀort decreased from 7.65-‐1.28 Auricular Branch transcutaneous VNS Steyn Interna5onal J of EM 2013:6;1-‐3, Prutchi 2013, cerbomed What about our COPD pa5ent? •  Tiotropium (Spiriva): • 
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Inhaled long-‐ac5ng an5-‐cholingeric bronchodilator is (rela5vely) new but is not for acute exacerba5ons NNTB=16 to prevent one exacerba5on •  Nebulized magnesium + B2-‐agonist: no eﬀect on FEV1 •  Inhaled steroids have no acute role •  Outpa5ent: reduced rate of decline in quality of life, possible reduced rate of decline in FEV1 •  Possible side eﬀects: thrush, hoarseness, risk of pneumonia Edwards et al, Yang et al Non-‐invasive ven5la5on for COPD •  462% increase 1998-‐2008 •  Currently used in up to 50% of all COPD pa5ents admined with acute respiratory failure •  60% reduc5on in risk of intuba5on (NNT 4) •  50% reduc5on in mortality risk (NNT 5) •  Mortality rate has declined overall •  Controversy for pa5ents who later require mechanical ven5la5on: increased mortality –  ?severity of disease or delay in intuba5on? Berg KM, Clardy P, Donnino MW. Noninvasive ven5la5on for acute respiratory failure: a review of the literature and current guidelines. Intern Emerg Med (2012)7:539-‐545 NIV: The Big Picture Berg KM, Clardy P, Donnino MW. Noninvasive ven5la5on for acute respiratory failure: a review of the literature and current guidelines. Intern Emerg Med (2012)7:539-‐545 References available as App 2013 COPD GOLD Guidelines$5.99 FREE Summary •  Protocolized asthma guideline use is recommended •  ED: Stress outpa5ent compliance to pa5ents and families •  Time to ED disposi5on, validated disposi5on decisions •  Give early steroids (<60 minutes) for acute moderate to severe asthma •  Consider nebulized magnesium for adults •  Non-‐invasive ven5la5on: great for COPD, possible beneﬁts for our asthma pa5ents with more data needed •  New stuﬀ on the Horizon References • 
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Berg KM, Clardy P, Donnino MW. Noninvasive ven5la5on for acute respiratory failure: a review of the literature and current guidelines. Intern Emerg Med (2012)7:539-‐545. Bhogal SK, McFillivray D, Bourbeau J, et al. Early administra5on of systemic cor5costeroids reduces hospital admission rates for children with moderate and severe asthma exacerba5on. Ann Emerg Med 2012 July(60)1: 84-‐91e3. Edwards L, Shirtcliﬀe P, Wadsworth K, et al. Use of nebulized magnesium sulfate as an adjuvant in the treatment of acute exacerba5ons of COPD in adults: a randomised double-‐blind placebo-‐controlled trial. Thorax 2013 Jan 7. doi:
10.1136/thoraxjnl-‐2012-‐202225. Papierniak ES, Lowenthal DT, Harman E. Novel therapies in asthma: leukotriene antagonists, biologic agents, and beyond. American Journal of Therapeu5cs 2013(20):79-‐103. Bruselle GG, Vanders5chele C, Jordens P, et al. Azithomycin for preven5on of exacerba5ons in severe asthma (AZISAST): a mul5centre randomised double-‐blind placebo-‐controlled trial. Thorax 2013 Jan 3. doi: 10.1136/
thoraxjnl-‐2012-‐202698. Shan Z, Rong Y, Yang W, et al. Intravenous and nebulized magnesium sulfate for trea5ng acute asthma in adults and children: A systemic review and meta-‐analysis. Respir Med 2013 Jan 3. pii: S0954-‐6111(12)00451-‐9. doi: 10.1016/j.rmed.2012.12.001. Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, Rowe BH, Smith BJ. Non-‐
invasive posi5ve pressure ven5la5on for treatment of respiratory failure due to severe acute exacerba5ons of asthma. Cochrane Database of Systema2c Reviews 2012, Issue 12. Art. No.: CD004360. DOI: 10.1002/14651858.CD004360.pub4. Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstruc5ve pulmonary disease. Cochrane Database of Systema2c Reviews 2012, Issue 7. Art. No.: CD009285. DOI: 10.1002/14651858.CD009285.pub2. Gorelick MH, Stevens MW, Schultz TR, et al. Performance of a Novel Clinical Score, The Pediatric Asthma Severity Score (PASS), in the Evalua5on of Acute Asthma. Acad Emerg Med 2004 11(1): 10-‐18 References • 
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Sellers, WFS. Inhaled and intravenous treatment in acute severe and life-‐threatening asthma. Bri5sh Journal of Anaesthesia 2013 (110) 2: 183-‐90. Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled cor5costeroids for stable chronic obstruc5ve pulmonary disease. Cochrane Database Syst Rev. 2012 Jul 11; 7:CD002991. doi:
10.1002/14651858.CD002991.pub3 Dexheimer JW, Abramo TJ, Arnold DH, et al. An asthma management system in a pediatric emergency department. Interna5onal Journal of Medical Informa5cs 2012, hnp://dx.doi.org/10.1016/j.ijmedinf.2012 Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a mul5centre, double-‐blind, placebo-‐controlled trial. The Lancet 2012 August 18(380): 651-‐659. Global Strategy for the Diagnosis, Management and Preven2on of COPD, Global Ini5a5ve for Chronic Obstruc5ve Lung Disease (GOLD) 2013. Available from: hnp://www.goldcopd.org Pediatric Asthma Score: hnp://www.childrenscolorado.org/pdf/2009-‐2010-‐Asthma-‐CCG.pdf Nannini LJ, Lasserson TJ, Poole P. Combined cor5costeroid and long-‐ac5ng B2agonist in one inhaler vs. long-‐ac5ng B2agonist for chronic obstruc5ve pulmonary disease. Cochrane Database of Systema2c Reviews 2012, Issue 9. Art. No.: CD006829. DOI: 10.1002/14651858.CD006829.pub2. Jat KR, Chawla D. Ketamine for management of acute exacerba5ons of asthma in children. Cochrane Database of Systema2c Reviews 2012, Issue 11. Art. No.: CD009293. DOI: 10.1002/14651858.CD009293.pub2. Non-‐invasive posi5ve pressure ven5la5on for acute respiratory failure: compara5ve eﬀec5veness. AHRQ Pub. No. 12-‐EHC089-‐3 September 2012.